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  • Review Article
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Complement in the immunopathogenesis of rheumatic disease

Nature Reviews Rheumatology volume 8, pages 458–468 (2012)Cite this article

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Abstract

The complement system has vital protective functions as a humoral component of the innate immune system and also through interactions with the adaptive immune system; however, when inappropriately activated or regulated, complement can cause inflammation and organ damage, and such processes are involved in the pathogenesis of many inflammatory conditions, not least rheumatic diseases. Furthermore, states of complement deficiency can predispose not only to infections, but also to autoimmune disorders, including rheumatic diseases such as systemic lupus erythematosus. In this Review, the mechanisms behind the pathogenic activities of complement in rheumatic diseases are discussed. Potential approaches to therapeutic intervention that focus on regulating complement activities in these disorders are also considered.

Key Points

  • Complement activation is involved in the pathogenesis of many rheumatic diseases

  • Deficiencies in components of the classical pathway of complement activation, but not other complement deficiencies, are associated with development of systemic lupus erythematosus (SLE) and SLE-like disorders

  • Complement activation via the alternative pathway in tissues can cause damage associated with autoimmune disease pathology

  • Increased knowledge of the functions of complement will hopefully lead to identification of new therapeutic targets in rheumatic diseases

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Figure 1: Schematic representation of complement activation and important interactions between complement components and cells.
Figure 2: Complement in the pathogenesis of SLE.
Figure 3: Complement in the pathogenesis of rheumatoid arthritis.

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Change history

  • 29 June 2012

    In the version of this article initially published online, Figure 1 incorrectly showed an arrow from C7 to C5b. This should have been a dashed line. The error has been corrected for the print, HTML and PDF versions of the article.

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Authors and Affiliations

  1. Department of Clinical Sciences, Section of Rheumatology, Lund University, Kioskgatan 3, Lund, SE-221 85, Sweden

    Gunnar Sturfelt

  2. Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University, Sölvegatan 23, Lund, SE-223 62, Sweden

    Lennart Truedsson

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G. Sturfelt and L. Truedsson contributed equally to researching data for the article, discussions of the content, writing the article and review and/or editing of the manuscript before submission.

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Correspondence to Gunnar Sturfelt.

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G. Sturfelt has acted as a consultant for Active Biotech. L. Truedsson declares no competing interests.

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Sturfelt, G., Truedsson, L. Complement in the immunopathogenesis of rheumatic disease. Nat Rev Rheumatol 8, 458–468 (2012). https://doi.org/10.1038/nrrheum.2012.75

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